Human Heterochromatin Protein 1α Promotes Nucleosome Associations That Drive Chromatin Condensation
Human Heterochromatin Protein 1α Promotes Nucleosome Associations That Drive Chromatin Condensation
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DOI：
10.1074/jbc.m113.512137
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发表时间：
2014-03-07
影响因子：
4.8
通讯作者：
Shogren-Knaak, Michael A.
中科院分区：
文献类型：
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作者：
Azzaz, Abdelhamid M.;Vitalini, Michael W.;Shogren-Knaak, Michael A.
背景：异染色质富含组蛋白 H3 (H3K9Me2/3) 的二甲基化和三甲基化赖氨酸 9 和异染色质蛋白 1 (HP1(Hs .))。结果：HP1(Hs) 与含有 H3K9Me3 的核小体阵列的关联促进了阵列压缩和跨阵列相互作用。结论：HP1(Hs) 关联引起阵列内和阵列间关联，导致染色质浓缩和成环。意义：对 HP1(Hs)-核小体相互作用的了解有助于了解异染色质的结构和功能。含有 HP1(Hs) 的异染色质位于染色体中心区域附近，调节 DNA 介导的过程，例如 DNA 修复和转录。异染色质的高级结构有助于这种调节，但异染色质的结构尚不清楚。我们采用多学科方法来确定 HP1(Hs)-核小体相互作用如何影响异染色质的结构。我们发现 HP1(Hs) 优先结合含有组蛋白 H3K9Me3 的核小体阵列，有利于非甲基化核小体阵列，并且非特异性 DNA 相互作用和预先存在的染色质压缩促进结合。 HP1(Hs) 的染色体和染色体阴影域在 HP1(Hs)-核小体相互作用中发挥重要作用，而铰链区的作用似乎不太重要。 HP1(Hs) 相关核小体阵列的电子显微镜显示 HP1(Hs) 引起阵列内的核小体关联，促进染色质凝聚。 HP1(Hs) 相关核小体阵列的差异沉降表明 HP1(Hs) 促进阵列之间的相互作用。这些链与链之间的相互作用得到了体内研究的支持，其中将果蝇同源物 HP1a 束缚到特定位点可促进与远处染色体位点的相互作用。我们的研究结果表明，HP1(Hs)-核小体相互作用会导致染色质浓缩，这是调节许多染色体事件的过程。
Background: Heterochromatin is enriched for di- and tri-methylated lysine 9 of histone H3 (H3K9Me2/3) and heterochromatin protein 1 (HP1(Hs .)). Results: The association of HP1(Hs) with H3K9Me3-containing nucleosome arrays facilitated array compaction and cross-array interactions. Conclusion: HP1(Hs) association caused intra- and inter-array associations, leading to chromatin condensation and looping. Significance: An understanding of HP1(Hs)-nucleosome interactions provides insights on the structure and functions of heterochromatin.HP1(Hs)-containing heterochromatin is located near centric regions of chromosomes and regulates DNA-mediated processes such as DNA repair and transcription. The higher-order structure of heterochromatin contributes to this regulation, yet the structure of heterochromatin is not well understood. We took a multidisciplinary approach to determine how HP1(Hs)-nucleosome interactions contribute to the structure of heterochromatin. We show that HP1(Hs) preferentially binds histone H3K9Me3-containing nucleosomal arrays in favor of non-methylated nucleosomal arrays and that nonspecific DNA interactions and pre-existing chromatin compaction promote binding. The chromo and chromo shadow domains of HP1(Hs) play an essential role in HP1(Hs)-nucleosome interactions, whereas the hinge region appears to have a less significant role. Electron microscopy of HP1(Hs)-associated nucleosomal arrays showed that HP1(Hs) caused nucleosome associations within an array, facilitating chromatin condensation. Differential sedimentation of HP1(Hs)-associated nucleosomal arrays showed that HP1(Hs) promotes interactions between arrays. These strand-to-strand interactions are supported by in vivo studies where tethering the Drosophila homologue HP1a to specific sites promotes interactions with distant chromosomal sites. Our findings demonstrate that HP1(Hs)-nucleosome interactions cause chromatin condensation, a process that regulates many chromosome events.